title: Cerulenin blockade of fatty acid synthase reverses hepatic steatosis in ob/ob mice.
abstract: Fatty liver or hepatic steatosis is a common health problem associated with abnormal liver function and increased susceptibility to ischemia/reperfusion injury. The objective of this study was to investigate the effect of the fatty acid synthase inhibitor cerulenin on hepatic function in steatotic ob/ob mice. Different dosages of cerulenin were administered intraperitoneally to ob/ob mice for 2 to 7 days. Body weight, serum AST/ALT, hepatic energy state, and gene expression patterns in ob/ob mice were examined. We found that cerulenin treatment markedly improved hepatic function in ob/ob mice. Serum AST/ALT levels were significantly decreased and hepatic ATP levels increased in treated obese mice compared to obese controls, accompanied by fat depletion in the hepatocyte. Expression of peroxisome proliferator-activated receptors α and γ and uncoupling protein 2 were suppressed with cerulenin treatment and paralleled changes in AST/ALT levels. Hepatic glutathione content were increased in some cases and apoptotic activity in the steatotic livers was minimally changed with cerulenin treatment. In conclusion, these results demonstrate that fatty acid synthase blockade constitutes a novel therapeutic strategy for altering hepatic steatosis at non-stressed states in obese livers.
authors.affiliation: Divisions of Transplant Surgery, Department of Surgery, Medical University of South Carolina, Charleston, South Carolina, United States of America.
authors.forename: Gang
authors.initials: G
authors.lastname: Cheng
authors.forename: Arun P
authors.initials: AP
authors.lastname: Palanisamy
authors.forename: Zachary P
authors.initials: ZP
authors.lastname: Evans
authors.forename: Alton G
authors.initials: AG
authors.lastname: Sutter
authors.forename: Lan
authors.initials: L
authors.lastname: Jin
authors.forename: Inderjit
authors.initials: I
authors.lastname: Singh
authors.forename: Harold
authors.initials: H
authors.lastname: May
authors.forename: Michael G
authors.initials: MG
authors.lastname: Schmidt
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Chavin
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D015152:Blotting, Northern; D001835:Body Weight; D002569:Cerulenin / Q000008:administration & dosage / Q000494:pharmacology*; D002849:Chromatography, Gas; D004305:Dose-Response Relationship, Drug; D054890:Fatty Acid Synthase, Type I / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005234:Fatty Liver / Q000188:drug therapy*; D020869:Gene Expression Profiling; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D051379:Mice; D008820:Mice, Obese; D047493:PPAR alpha / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism
chemical_list: D047493:PPAR alpha; D047495:PPAR gamma; D002569:Cerulenin; D054890:Fatty Acid Synthase, Type I; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase